Process and apparatus for dispensing liquid compositions intended for parenteral administration

ABSTRACT

An injection syringe is charged with liquid to be dispensed prior to attachment of the needle by mating the filling end of the syringe to the outlet valve of a propellent-pressurized container of the liquid. The liquid is dispensed as a solid stream (i.e., in &#39;&#39;&#39;&#39;plug flow&#39;&#39;&#39;&#39;) unaccompanied by any propellent. One way of achieving this is by using a propellent which is insoluble in the dispensable liquid. Another method would employ a double contianer. Thus, the liquid within the pressurized container can be kept separate from the propellent, e.g., by means of an impervious barrier in the form of a flexible bag containing the liquid to be dispensed. Alternatively, the container itself can be a cylinder of glass or other suitable material fitted at the bottom with a rubberlike septum. This septum separates the dispensable liquid from the propellent and is forced upward like a plunger or piston when the valve is opened. The upper portion of the container would hold the dispensable liquid. The chamber on the other side of the plunger or piston houses the propellent. The discharge end is hermetically fitted to the outlet valve of the pressurized container. Upon releasing the valve, the pure liquid is forced out of the pressurized container and into the barrel of the syringe at a rate determined by the pressure of the propellent.

O v Umted States Patent; [1 1 [111 3,853,157

Madaio Dec. 10, 1974 PROCESS AND APPARATUS FOR pensed prior to attachment of the needle by mating DISPENSING LIQUID COMPOSITIONS the filling end of the syringe to the-outlet valve of a INTENDED FOR PARENTERAL propellent-pressurized container of the liquid. The liq- ADMINISTRATION uid is dispensed as a solid stream (i.e., in plug flow) unaccompanied by any propellent. One way of achiev- [76] Inventor: Anthony M 27 Desmond ing this is by using a propellent which is insoluble in Bronxvlne 10708 the dispensable liquid. Another method would employ 22 Filed; 22, 1973 a double contianer. Thus, the liquid within the pressurized container can be kept separate from the pro- [21] Appl' 334,959 pellent, e.g., by means of an impervious barrier in the form of a flexible bag containing the liquid to be dis- 52 US. 141/2, 141/27, 141/370 p Alternatively, the container itself can be a y 51 Im. B65b 3/10 inder of glass or other suitable material fitted at the 58 Field of Search......... 141/2, 3, 26, 27, 20, 370; bottom with a rubberlike septum This septum p 123/215; 23/253 259 rates the dispensable liquid from the propellent and is forced upward like a plunger or piston when the valve 55 References Cited is opened. The upper portion of the container would UNITED STATES PATENTS hold the dispensable liquid. The chamber on the other side of the plunger or piston houses the propellent.

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ln loading hypodermic syringes with liquids intended for parenteral administration, i.e., intended for injection into the body through a hollow, skin-piercing needle, it had heretofore been the common practice to first assemble the components of the empty sterile syringe (i.e., needle, barrel and plunger) with the plunger fully depressed. For glass ampules or other single dose containers, the tip of the needle is submerged in the liquid and the plunger is then withdrawn, thereby drawing liquid up into the barrel of the syringe. Although this procedure has been in widespread use for many years, the methodsuffers from a number of drawbacks. For one thing, the force by which the liquid is drawn up through the needle and into the syringe barrel, namely, the vacuum incrementally formed with the barrel as the plunger is withdrawn, will draw in enviromen'tal atmospheric air. This presents a possible source of contamination, for example, in the form of air-borne microorganisms and particulate matter. Also, the breaking of the glass ampule can cause glass particles to fall into the ampule, in which case they can be drawn into the syringe with the liquid medication and subsequently injected into the patient.

One of the methods developed for attempting to cope with this problem has been the use of liquid reservoirs or containers capped with a rubberlike septum or diaphragm which is self-sealing after penetration by and withdrawal of the needle portion of the syringe. Although the use of a septum undoubtedly protects the reservoir from airborne contaminants to some extent, the degree of protection is far from complete since contamination can still occur by virtue of the repeated physical penetration through the septum and into the reservoir by the needle itself and possible corring of the rubberlike septum. Also, the edge of the needle can be burred by the septum as the former is pushed into the container. Prior to removal of the liquid medication from the dispensing container, the syringe must be filled with a volume of atmospheric air equal to the volume of the liquid medication being withdrawn. Air is thereby injected into the container each time medication is removed. Furthermore, the self-sealing ability of I the septum deteriorates with repeated penetration due to a degeneration in the integrity of the septum mate rial.

Another method of parenteral administration of liquids which has been developed in order to minimize the problem of contamination has been to pre-package the liquids in small vials which provide one or a few dosages. This expedient, albeit more sanitary, still suffers fromyet another disadvantage inherent to most previously known methods for loading syringes. In particular, during the filling step, it has been necessary to withdraw the plunger'of the syringe carefully and at a slow rate with the orifice of the needle constantly submerged below the surface of the liquid in order to prevent entrainment of air bubbles within the syringe. To avoid this particular problem, a variant of the small vial approach has been used which entails the use of disposable syringes pre-packaged with liquid already in them for one-shot" injection after which the spent syringes are thrown away. However, this expedient, like the one previously mentioned is wasteful of materials and tends to discourage the shipment and storage of liquids in bulk form. As a result, the use of small vials or disposable syringes represents an undesirable added cost factor, particularly in places such as hospitals and clinics where parenteral administration of liquid medication is carried out routinely on a large scale. Therefore a need has existed for loading hypodermic syringes which avoids the aforementioned difficulties.

Accordingly, it is an object of the present invention to provide an improved method and apparatus for filling injection syringes with liquids intended for parenteral administration.

Another object is to provide an improved method and apparatus for filling injection syringes with liquids without risk of contamination by exposure of the liquid to foreign substances or organisms that are air-borne.

Yet another object is to provide an improved method and apparatus for filling injection syringes with liquids at a convenient rate without entrainment of atmospheric air within the filled chamber.

These and other objects of the present invention as well as the advantages thereof can be had by reference to the following detailed description, drawings and claims.

SUMMARY OF THE lNVENTlON The foregoing objects are achieved according to the present invention by an apparatus and process whereby a syringe, e.g., a hypodermic needle is loaded quickly, sanitarily and with minimum risk of entraining atmospheric air within the chamber or barrel of the syringe.

According to the process of the invention, a hypodermic" syringe to be used for injecting liquids into the body and comprising a barrel, plunger and hollow injection needle is filled with the liquid to be administered by engaging the filling tip of the barrel with the outlet of a pressurized can or container of liquid to be dispensed. The filling tip of the syringe and the outlet of the container are engaged hermetically so that a fluid-tight seal between the two components results, thereby ensuring against leakage of liquid at this point during the dispensing step. The pressurized container of liquid is fitted with a plug or closure and a valve to contain the pressurized contents and regulate the amount of liquid dispensed to the syringe. The container is further characterized in its design so that only the liquid to be dispensed is propelled from the container when the valve is opened.

Upon opening the valve, only the dispensable liquid is forced through the outlet of the container into the filling tip of the syringe. The pressure within the container causes the liquid entering the syringe through the filling tip to push back the plunger, thereby filling the barrel with liquid. The valve on the container is kept open, either manually or automatically, until the desired quantity of liquid has filled the syringe. At this point, the valve is closed, shutting off the flow-of liquid from the container. Then, the filling tip of the syringe is disengaged from the outlet of the container and the injection needle is attached to the filling tip of the syringe, whose liquid contents are now ready for parenteral administration. The valve outlet is equipped with a shield which can be closed so that the container can be stored for future syringe-filling operations.

Further features of the method of this invention are presented below in connection with the apparatus associated therewith, which comprises, in combination, a container for the dispensable liquid, a closure and valve for the container which are fitted with an outlet and a hypodermic syringe comprising a barrel and a plunger. One end of the barrel is adapted to serve as the filling tip of the syringe when the injection needle is not in place. In the apparatus of the invention, the filling tip of the syringe is mated with the outlet of the container to give a fluid-tight seal to prevent leakage of liquid during the dispensing or filling process of the invention.

The container for the liquid to be dispensed is adapted for storage of the liquid therein under pressure. Pressurization of the container is achieved during its manufacture by introducing a suitable pressurizing agent or propellent, e.g., a gas or liquified gas, into the container along with the liquid to be dispensed. Accordingly, the container is desirably constructed of a rigid material such as metal or glass, subject to the proviso that the portions of the container which come into contact with the contents are of materials which are inert to those contents or specially treated so that corrosion or formation of harmful products within the container are avoided. Alternatively, when the dispensible liquid is kept in an impervious inner container as described hereinbelow, there can be added to the propellent in the outer container one or more suitable corrosion inhibitors which do not come into contact with the dispensable liquid.

The use of glass in constructing the container for the dispensible liquid is advantageous when it is desired to monitor the amount of dispensable liquid remaining in the container by visual inspection. Glass containers also facilitate inspection of the medication for particulate matter.

It is a feature of the present invention that the container, closure and valve are designed to permit only the dispensable liquid and not the propellent to be discharged from the container into the syringe. One way of achieving this is to select a propellent composition which is essentially insoluble in the dispensable liquid so that a two-phase (liquid-gas) or three phase (liquidliquid-gas) system is established within the container, one phase being the dispensable liquid and the other phase or phases being the propellent. The dispensable liquid phase will be above, below or between the propellent phase or phases depending on the density of the dispensable liquid relative to that of the propellent. Thus, when the propellent is a gas, the dispensable liquid will normally form the lower of the two phases (liquid-gas). When the propellent is a liquified gas of the type described in further detail hereinafter, the dispensable liquid will form the lowest of the two liquid phases in the three-phase (liquid-liquid-gas) system if the liquid propellent is less dense than the dispensable liquid. If the dispensable liquid is less dense than the liquid propellent, then the dispensable liquid will form the upper of the two liquid phases.

The closure and valve of the container are designed so that when the valve is opened, egress is provided only for the dispensable liquid by means of a hollow open-ended portion (dip-tube") of the closure which extends or projects into the container to a point within the phase corresponding to the dispensable liquid.

In a preferred aspect of the present invention, the requisite separation between the propellent and the dispensable liquid is achieved by utilizing one of three methods: (1) using a propellent which is insoluble in the liquid medication; (2) using a container within a container, the inner container being a collapsible bag or bladder holding the dispensable liquid out of contact with the propellent which is in the outer container, as described,for example, in U.S. Pat. No. 2,937,791; and (3) the use of a cylindrical container, the top portion being hermetically sealed to the closure and valve, and the bottom end having an impermeable rubberlike sep' tum or portion adapted to slide upward within the cylinder like a piston when the valve is opened. This occurs because of the pressure exerted on the septum by the propellent as described, for example in U.S. Pat. No. 3,407,974. The cylindrical container is desirably, but not necessarily, made of glass. The propellent occupies the space between the rigid wall of the container and the outer surface of the bag or below the piston at the bottom of the glass cylinder. The closure and valve of the container are designed so that a hollow, openended portion of the closure extends or projects into the bag or glass cylinder, the neck of the bag or glass cylinder being permanently and hermetically sealed to the inwardly projecting portion of the closure. When the valve is opened, only the contents of the bag or the top portion of the glass cylinder, i.e., the dispensable liquid, are expelled from .the container through the inwardly projecting portion of the closure to the outlet of the container. Both the collapsible bag which is made of a flexible material and the glass cylinder must be chemically inert and physically impervious to both propellent and dispensable liquid, thereby forming an inpenetrable barrier between the two substances. The hermeticseal between the inwardly projecting portion of the closure and the neck of the bag or glass cylinder surrounding this portion contributes to the fluid-tight integrity of the separation between propellent, dispensable liquid and atmospheric air. When the valve is opened, the pressure of the propellent acts on the bag or piston at the bottom of the glass cylinder to expel the dispensable liquid alone from the container. The bag, being flexible, collapses to the extent that liquid is removed therefrom. Likewise, the volume of upper portion of the glass cylinder decreases due to the upward movement of the piston. Since the container is manufactured so that either the bag or upper portion of the glass cylinder is initially completely filled with dispensable liquid, the gradual collapse or shrinkage of the bag or decrease in volume of the glass cylinder during the practice of the method of this invention ensures that all of the space within the bag or glass cylinder at any time is occupied by the dispensable liquid and that only this liquid is dispensed from the outlet of the container from the instant the valve is opened. This feature is critical to the success of the present invention, since the present method would be defeated if gaseous materials were to be expelled along with the dispensable liquid which is the case, for example, in U.S. Pat. No.

3,220,413; US. Pat. No. 3,540,448 and US. Pat. No. 3,656,482.

Since the propellent is not consumed during the lifetime of the container, it is possible to use a bag for the dispensable liquid which, when filled, occupies most of or substantially fills the space within the rigid container. The remaining space need only be sufficient to contain enough propellent to establish and maintain the desired propellent pressure. Furthermore, the use ofa bag to contain the dispensable liquid in the manner described hereinabove permits holding the container in any convenient position when discharging the liquid.

The materials of which the bag can be constructed consistent with the aforementioned requirements include films of rubber or polyolefins, e.g., polyethylene.

The rate of flow of dispensable liquid from the container into the syringe depends to a large extent on the pressure exerted by the propellent system within the container. Propellent pressures suitable for use in the present invention are in turn determined by the proper selection of propellent gases and/or liquified gas. When a compressed gas, e.g., nitrogen and liquified lower alkanes such as propane, is used as the propelling agent, the pressure established within the container depends primarily on the concentration of the gas. On the other hand, when liquified gases are used, the pressure established will depend on the vapor pressure of the liquified gas. In this connection, the use of liquified gases possesses the advantage that the pressure within the container remains constant during the gradual exhaustion of the dispensable liquid as long as at least one drop of liquified gas remains in the container. In this way, the rate of discharge of dispensable liquid from the container remains constant during the lifetime of the container. On the other hand, propellents made up entirely of pressurized gas will experience a gradual decrease in pressure and consequent decrease in rate of flow of dispensable liquid due to the increasing volume occupied by the propellent gas as the contents of the bag become exhausted and the bag collapses.

Liquifiable gases suitable for use in the present invention include normally gaseous chlorofluoroalkane propellents such as dichlorodifluoromethane, CCl F mixtures of dichlorodifluoromethane with dichlorotetrafluoro-ethane, (CClF and mixtures of dichlorodifluoromethane with monochlorodifluoroethane, CClF CH The requisite pressure within the container can be achieved by selecting the proper relative amounts of the aforementioned liquifiable gaseous propellents as disclosed, for example, in Soap and Sanitary Chemicals, 29(9), 142, 147(1953).

The closure and valve, like the other portions of the container, are constructed of materials which, to the extent that they come into contact with the dispensable liquid, are chemically inert thereto. Valves suitable for use according to the present invention can be of the manually operated type. Alternatively, the valve can be of the automatic shut-off variety whereby a predetermined fixed quantity of liquid can be dispensed to the syringe. The use ofa metered valve is an advantage, for example. when rapid filling of a large number of syringes is desired within a minimum period of time.

If desired, a filter can be interposed in the path of the dispensable liquid at some convenient point in the closure, valve or outlet to guard against the escape of any particulate matter which might be present in the container and which might otherwise find its way-into the syringe. The closure, valve and outlet assemblies of the container can be adapted to receive a cover or shield to protect these components, especially the valve mechanism, from dust when the container is not in use. The shield or cover can be permanently affixed to the outlet (discharge chamber) so as to allow any size syringe to enter. This type of shield is desirably adapted to receive a removable cap which is replaced when the apparatus is not in use. The shield is also desirably constructed to permit routine cleaning thereof with an antiseptic such as alcohol.

It is a prime desideratum of this invention that the outlet of the container be adapted to hermetically and removeably engage the filling tip of the syringe component of the present apparatus. In conventional hypodermic syringes which are suitable for use in the present invention, the filling tip on the barrel is often of the type depicted in the accompanying drawings. With this type of filling tip, the outlet of the container for the dispensable liquid would form a discharge chamber which would be force-fitted over the filling tip of the syringe barrel in the same way that the injection needle would be fitted over the filling tip after the barrel has been filled according to the method of this invention. In addition to discharge chamber-filling tip combinations of the force-fitted type, other designs can be employed, such as where the filling tip of the syringe and the discharge chamber are provided with screw threads Luer- Lok) or adapted to be snapped together to form the requisite fluid-tight seal.

The apparatus and method of the present invention has numerous advantages not possessed or obtainable with conventional arrangements. Thus, since the container for the dispensable liquid is never penetrated by foreign bodies during its lifetime, there is no danger of contamination of the liquid to be dispensed from air borne bacteria, particulate matter, and the like. Accordingly, the contents of the container can be kept sterile and the quantities of dispensable liquid which can be stored are much larger than heretofore permitted in conventional containers, whose contents are repeatedly exposed to the atmosphere during syringefilling operations. Furthermore, since the propellent is not consumed during the lifetime of the container, only the dispensable liquid need be replaced and this can be done repeatedly provided conditions of sterility are maintained during each refilling operation.

DESCRIPTION OF THE DRAWINGS Referring now to the drawings,

FIG. 1 is a vertical sectional view of an embodiment of the apparatus of the invention showing the relative placement of the components thereof.

FIG. 2 is a vertical sectional view of a conventional syringe (minus the needle component) whose relative position in the apparatus is shown in phantom in FIG. 1.

FIGS. 3 through 8 are a series of vertical sectional views representing the principal steps involved in using the present apparatus according to the process of the invention.

With particular reference to FIG. 1, an outer can 1 is constructed of a rigid material, for example, metal or glass, which is capable of withstanding the positive pressure exerted by the propellent 2 contained between the outer can and flexible bag 5. The flexible bag 5 is made of a suitable material such as polyethylene or the like and contains liquid composition 6 which is intended for parenteral administration.

The neck of the flexible bag is permanently attached to the depending end of a plug 7 which is contained within cap 3. The neck of flexible bag 5 forms thereby an hermetic or fluid-tight seal with plug 7. The plug 7 is made ofa plastic rubberlike or silicone-coated material such that the plug is permanently positioned within the cap 3 by force-fitting the plug into the widened upper portion 27 of the cap.

The plug 7 has a central bore 9 in which is slidably mounted the discharge valve stem 11. The lower end of the valve stem 11 is flared outwardly to form a tapered segment 13 which cooperates with the corresponding tapered countersunk cavity 15 in the bottom of plug 7. Tapered segment 13 is fitted to valve stem 11 by means of a threaded protuberance 38 on the tapered segment which engages a corresponding threaded hole in the bottom of valve stem 11. The tapered segment 13 forms a fluid tight cut-off when the valve stem 11 is held in the up position by the compression spring 17 which surrounds the valve stem within a recess 19 formed by enlarging the central bore 9. The upper end of the spring 17 abuts against enlarged portion 21 of valve stem 11 which in turn abuts against the bottom surface of-valve head 29. The valve head 29 is advantageously made of metal and is secured to the top of plug 7 by engagement with the threaded upper portion 31 of cap portion 3.

The upper end of the valve stem 11 is connected to a button 33 by means of a threaded protuberance 35 which engages a correspondingly threaded hole in the top of the valve stem. Upon depressing the button 33, the valve stem 11 moves to the down" position shown in phantom and exposes inlet port 36 in valve stem 11 to liquid composition 6. Then as a result of the pressure exerted by propellent 2, the liquid composition 6 enters inlet port 36, flows up through channel 37 within valve stem 11 and out of exit port 39 which is now exposed to the outside through orifice 41. The sliding interface between valve head 29 and valve stem 11 is sealed to prevent leakage of liquid 6 between the two sliding surfaces by means of a flexible O ring 23 which surrounds valve stem 11 within the recess 24 formed by enlarging the central bore 9.

When the liquid composition 6 leaves the container through exit orifice 41, it does so under pressure and enters the filling end of syringe 46 which is shown in phantom position as it would appear during the practice of the present invention.

In FIG. 2, there is depicted a syringe 46 ofa type suitable for use in the present invention from which the injection needle has been removed. The cylindrical barrel 47 of syringe 46 can be made of a suitable molded plastic material, e.g., polyethylene. The barrel 47 of syringe 46 reduces at the front end to a hollow tapered filling tip 45 which mates with the corresponding tapered female butt end of the needle (not shown) to give a fluid-tight squeeze fit.

During the practice of the invention, filling tip 45 of syringe 46 mates with the correspondingly tapered discharge chamber 43 of valve head 29 to give a fluid-tight squeeze fit as shown in phantom in FIG. 1. Upon depressing button 33, liquid is discharged from exit orifice 41 directly into inlet orifice 49 of filling tip 45. Because of the close fit between filling tip 45 and discharge chamber 43, there is no escape of liquid to the outside during the filling operation.

Referring to FIG. 2, the liquid entering inlet orifice 49 under pressure exerts a force on the front end of plunger 51 which is slideably mounted within barrel 47. The force exerted by the liquid pushes plunger 51 out of the filling chamber 53 causing the chamber to become filled with liquid. Flared portions 55 and 57 of the barrel 47 and plunger 51 respectively provide gripping surfaces for the operators fingers during parenteral administration of the liquid composition from the syringe. I

Referring to FIGS. 3 through 8, FIG. 3 shows filling can 1 and syringe 46 at the commencement of the filling process according to the present invention prior to the engagement of discharge chamber 43 with filling tip 45. At this point, the button 33 is in the up or closed position. FIG. 4 shows discharge chamber 43 and filling tip 45 in engagement ready for dispensing of liquid 6 upon depressing button 33.

FIG. 5 shows the dispensing of liquid 6 into the sy ringe 46 with the button 33 in the down" or open position. During this stage of the process, the volume of liquid 6 in the flexible bag 5 decreases to the same extent that the liquid fills the syringe 46. FIG. 6 shows the apparatus of the inventionat that stage in the process when the syringe 46 has been filled with the desired amount of liquid composition 6. At this point, the button 33 is released, whereupon it returns to the *up" or closed position. FIG. 7 shows the syringe 46 filled with the desired amount of liquid 6 and the filling tip 45 withdrawn from engagement with discharge chamber 43. FIG. 8 shows the liquid-filled syringe fitted with an injection needle ready for administering the liquid 64.

The accompanying drawings and foregoing specification have described the present invention in a preferred form. However, it will be understood that modifications and changes can be made without departing from the scope of the invention which is defined in the appended claims.

I claim:

1. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid container having an opening at one end and adapted to contain under pressure the liquid composition and a gas or liquified gas essentially insoluble in the liquid composition, a closure for the opening having a portion adapted to project into the dispensible'liquid composition in the container, a valve within the closure for discharging the liquid composition from the container through the inwardly projecting portion of the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.

2. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid cylindrical container having an opening at the top end and sealed at the bottom end and adapted to contain the liquid composition and a gas or liquified gas propellent under positive pressure, a closure for the opening, a partition dividing the container into a top portion and a bottom portion, said partition being slideably disposed within the container and adapted to provide an impervious barrier between the propellent in the bottom portion of the container and the liquid composition in the top portion of the container, a valve within the closure for discharging the liquid composition from the top portion of the container through the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.

3. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid container having an opening at one end and adapted to contain the liquid composition and a gas or liquified gas under positive pressure, a closure for the opening having a portion projecting into the container, a bag of flexible material ofa size when filled with the liquid composition to substantially fill the container and adapted to provide an impervious barrier between the gas or liquified gas and the liquid composition and said bag having a neck portion hermetically surrounding the inwardly projecting portion of the closure, a valve within the closure for discharging the liquid composition from the bag through the inwardly projecting portion of the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.

4. An apparatus according to claim 3 wherein the valve is adapted to discharge a predetermined fixed amount of liquid composition from the bag through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe.

5. An apparatus according to claim 3 wherein the outlet of the container is a chamber adapted to be removeably force fitted over the hollow filling tip of the syringe to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe.

6. An apparatus according to claim 3 wherein the closure for the opening in the container has a bore leading from the interior of the flexible bag to the exterior of the closure, said bore having the operating member of the valve slideably and hermetically disposed therein and extending from the portion of the closure projecting into the container to a point exterior to the closure, said operating member of the valve having a conduit therein to provide communication between the interior of the bag and the outlet of the container when the valve is opened, said valve being opened and closed by the sliding movement of the operating member of the valve.

7. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of:

a. hermetically engaging the hollow filling tip of a hypodermic syringe directly with the outlet of a container having an opening at one end and containing under positive pressure the liquid composition and a gas or liquified gas essentially insoluble in the liquid composition, a closure for the opening having a portion projecting into the dispensable liquid composition in the container, a valve within the closure for discharging the liquid composition from the container through the inwardly projecting portion of the closure to the outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel;

b. opening the valve to discharge the liquid composition from the container through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syringe;

c. continuing step (b) until the barrel of the syringe has been filled with a desired volume of liquid composition;

d. closing the valve; and

e. disengaging the filling tip of the syringe from the outlet of the container.

8. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of;

a. hermetically engaging the hollow tip of a hypodermic syringe directly with the outlet of a rigid cylindrical container having an opening at the top end and sealed at the bottom end and adapted to contain the liquid composition and a gas or liquified gas propellent under positive pressure, a closure for the opening, a partition dividing the container into a top portion and a bottom portion, said partition being slideably disposed within the container and adapted to provide an impervious barrier between the propellent in the bottom portion of the container and the liquid composition in the top portion of the container, a valve within the closure for discharging the liquid composition from the top portion of the container through the closure to the outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel;

. opening the valve to discharge the liquid composition from the container through the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syringe;

c. continuing step (b) until the barrel of the syringe has been filled withina desired volume of liquid composition;

d. closing the valve; and

e. disengaging the filling tip of the syringe from the outlet of the container.

9. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of:

a. hermetically engaging the hollow tip of a hypodermic syringe directly with the outlet of a container having an opening at one end and adapted to contain a gas or liquified gas under positive pressure, a closure for the opening having a portion projecting into the container, a bag of flexible material of a size when filled with liquid composition to substantially fill the container and adapted to provide an impervious barrier between the gas or liquified gas and the liquid composition and said bag having a neck portion hermetically surrounding the inwardly projecting portion of the closure, a valve within the closure for discharging the liquid composition from the bag through the inwardly projecting portion of the closure to an outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel;

. opening the valve to discharge the liquid composition from the bag through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syringe;

c. continuing step (b) until the barrel of the syringe has been filled with a desired volume of liquid composition; v

d. closing the valve; and

e. disengaging the filling tip of the syringe from the outlet of the container.

10. A method according to claim 9 wherein the valve is adapted to discharge a predetermined fixed amount of liquid composition from the bag through the inwardly projecting .portion of the closure to the outlet of the container and into the barrel of the syringe.

11. A method according to claim 9 wherein the outlet of the container is a chamber adapted to be removeably force fitted over the hollow filling tip of the syringe to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe.

12. A method according to claim 9 wherein the closure for the opening in the container has a bore leading from the interior of the flexible bag to the exterior of the closure, said bore having the operating member of thevalve slideably and hermetically disposed therein and extending from the portion of the closure projecting into the container to a point exterior to the closure, said operating member of the valve having a conduit therein to provide communication between the interior of the bag and the outlet of the container when the valve is opened, said valve being opened and closed by the sliding movement of the operating member of the valve. 

1. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid container having an opening at one end and adapted to contain under pressure the liquid composition and a gas or liquified gas essentially insoluble in the liquid composition, a closure for the opening having a portion adapted to project into the dispensible liquid composition in the container, a valve within the closure for discharging the liquid composition from the container through the inwardly projecting portion of the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.
 2. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid cylindrical container having an opening at the top end and sealed at the bottom end and adapted to contain the liquid composition and a gas or liquified gas propellent under positive pressure, a closure for the opening, a partition dividing the container into a top portion and a bottom portion, said partition being slideably disposed within the container and adapted to provide an impervious barrier between the propellent in the bottom portion of the container and the liquid composition in the top portion of the container, a valve within the closure for discharging the liquid composition from the top portion of the container through the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.
 3. An apparatus for dispensing a liquid composition intended for parenteral administration comprising in combination a rigid container having an opening at one end and adapted to contain the liquid composition and a gas or liquified gas under positive pressure, a closure for the opening having a portion projecting into the container, a bag of flexible material of a size when filled with the liquid composition to substantially fill the container and adapted to provide an impervious barrier between the gas or liquified gas and the liquid composition and said bag having a neck portion hermetically surrounding the inwardly projecting portion of the closure, a valve within the closure for discharging the liquid composition from the bag through the inwardly projecting portion of the closure to an outlet of the container, and a hypodermic syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in a hollow filling tip hermetically engaged directly with the outlet of the container to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe and a plunger slideably disposed within the barrel and responsive to the pressure exerted by the liquid composition entering the barrel of the syringe.
 4. An apparatus according to claim 3 wherein the valve is adapted to discharge a predetermined fixed Amount of liquid composition from the bag through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe.
 5. An apparatus according to claim 3 wherein the outlet of the container is a chamber adapted to be removeably force fitted over the hollow filling tip of the syringe to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe.
 6. An apparatus according to claim 3 wherein the closure for the opening in the container has a bore leading from the interior of the flexible bag to the exterior of the closure, said bore having the operating member of the valve slideably and hermetically disposed therein and extending from the portion of the closure projecting into the container to a point exterior to the closure, said operating member of the valve having a conduit therein to provide communication between the interior of the bag and the outlet of the container when the valve is opened, said valve being opened and closed by the sliding movement of the operating member of the valve.
 7. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of: a. hermetically engaging the hollow filling tip of a hypodermic syringe directly with the outlet of a container having an opening at one end and containing under positive pressure the liquid composition and a gas or liquified gas essentially insoluble in the liquid composition, a closure for the opening having a portion projecting into the dispensable liquid composition in the container, a valve within the closure for discharging the liquid composition from the container through the inwardly projecting portion of the closure to the outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel; b. opening the valve to discharge the liquid composition from the container through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syringe; c. continuing step (b) until the barrel of the syringe has been filled with a desired volume of liquid composition; d. closing the valve; and e. disengaging the filling tip of the syringe from the outlet of the container.
 8. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of; a. hermetically engaging the hollow tip of a hypodermic syringe directly with the outlet of a rigid cylindrical container having an opening at the top end and sealed at the bottom end and adapted to contain the liquid composition and a gas or liquified gas propellent under positive pressure, a closure for the opening, a partition dividing the container into a top portion and a bottom portion, said partition being slideably disposed within the container and adapted to provide an impervious barrier between the propellent in the bottom portion of the container and the liquid composition in the top portion of the container, a valve within the closure for discharging the liquid composition from the top portion of the container through the closure to the outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel; b. opening the valve to discharge the liquid composition from the container through the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syrinGe; c. continuing step (b) until the barrel of the syringe has been filled within a desired volume of liquid composition; d. closing the valve; and e. disengaging the filling tip of the syringe from the outlet of the container.
 9. A method of dispensing a liquid composition intended for parenteral administration comprising the steps of: a. hermetically engaging the hollow tip of a hypodermic syringe directly with the outlet of a container having an opening at one end and adapted to contain a gas or liquified gas under positive pressure, a closure for the opening having a portion projecting into the container, a bag of flexible material of a size when filled with liquid composition to substantially fill the container and adapted to provide an impervious barrier between the gas or liquified gas and the liquid composition and said bag having a neck portion hermetically surrounding the inwardly projecting portion of the closure, a valve within the closure for discharging the liquid composition from the bag through the inwardly projecting portion of the closure to an outlet of the container, said syringe comprising a barrel of constant diameter having an opening at one end and terminating at the other end in the hollow filling tip and a plunger slideably disposed within the barrel; b. opening the valve to discharge the liquid composition from the bag through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe which is further characterized in that the plunger slideably disposed within the barrel is responsive to the pressure exerted by the liquid composition entering the barrel of the syringe; c. continuing step (b) until the barrel of the syringe has been filled with a desired volume of liquid composition; d. closing the valve; and e. disengaging the filling tip of the syringe from the outlet of the container.
 10. A method according to claim 9 wherein the valve is adapted to discharge a predetermined fixed amount of liquid composition from the bag through the inwardly projecting portion of the closure to the outlet of the container and into the barrel of the syringe.
 11. A method according to claim 9 wherein the outlet of the container is a chamber adapted to be removeably force fitted over the hollow filling tip of the syringe to form a fluid-tight conduit for the liquid composition from the outlet to within the barrel of the syringe.
 12. A method according to claim 9 wherein the closure for the opening in the container has a bore leading from the interior of the flexible bag to the exterior of the closure, said bore having the operating member of the valve slideably and hermetically disposed therein and extending from the portion of the closure projecting into the container to a point exterior to the closure, said operating member of the valve having a conduit therein to provide communication between the interior of the bag and the outlet of the container when the valve is opened, said valve being opened and closed by the sliding movement of the operating member of the valve. 